Printed on: Fri Jan 05 2024, 09:25:32 PM(EST) Status: Currently Official on 06-Jan-2024 DocId: GUID-D3E02FCD-414B-4B50-BE18-05CE317D56B0_4_en-US
Printed by: USP NF Official Date: Official as of 01-Apr-2023 Document Type: USP @2024 USPC
Do Not Distribute DOI Ref: rx8t8 DOI: https://doi.org/10.31003/USPNF_M41925_04_01
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Suitability requirements
Iohexol Injection Resolution: NLT 20.0 between iohexol related
To view the Notice from the Expert Committee that posted in compound A and iohexol related compound C
conjunction with this accelerated revision, please click Analysis
www.uspnf.com/rb-iohexol-inj-20230331. Sample: Sample solution
Excluding peaks with retention times between 0.84
DEFINITION (relative to the endo-isomer of iohexol, which is the first
Iohexol Injection is a sterile solution of Iohexol in Water for main peak) and 1.0, calculate the percentage of
Injection. It contains NLT 95.0% and NMT 105.0% of the O-alkylated compounds and any other individual impurity
labeled amount of iohexol (C19H26I3N3O9) as organically peak, in the portion of Iohexol taken:
bound iodine. It may contain small amounts of suitable
buffers and Edetate Calcium Disodium as a stabilizer. Iohexol Result = (r U/r T) × 100
Injection intended for intravascular or intrathecal use
contains no antimicrobial agents. rU = peak response of each impurity
rT = sum of all the peak responses
IDENTIFICATION
• A. The retention times of the major peaks of the Sample Acceptance criteria
solution correspond to those of the System suitability Individual impurity: NMT 0.6% of O-alkylated
solution, as obtained in the test for Organic Impurities. compounds; NMT 0.1% of any other individual impurity
ASSAY Total impurities: NMT 0.3%, excluding O-alkylated
• PROCEDURE compounds
Sample: A volume of Injection equivalent to 300 mg of SPECIFIC TESTS
al
iodine • BACTERIAL ENDOTOXINS TEST á85ñ: NMT 0.2 USP Endotoxin
Analysis: Transfer the Sample to a glass-stoppered, 250-mL Unit per 50 mg of iodine
conical flask. Add 25 mL of 1.25 N sodium hydroxide and • PH á791ñ: 6.8–7.7
500 mg of powdered zinc, connect the flask to a reflux • PARTICULATE MATTER IN INJECTIONS á788ñ: The Injection
condenser, and reflux the solution for 1 h. Cool the flask to
ci labeled for intrathecal use meets the requirements for
room temperature, rinse the condenser with 20 mL of small-volume injections.
water, disconnect the flask from the condenser, and filter • FREE IODIDE: Transfer 5.0 mL of Injection to a suitable
the mixture. Rinse the flask and the filter thoroughly with container, add 20 mL of water, and titrate with 0.001 N
small portions of water, adding the rinsings to the filtrate. silver nitrate VS using a silver electrode in combination with
Add 5 mL of glacial acetic acid, and titrate with 0.1 N silver an appropriate reference electrode. Each mL of 0.001 N
nitrate VS. Each mL of 0.1 N silver nitrate is equivalent to
ffi
silver nitrate is equivalent to 0.1269 mg of iodine.
27.37 mg of C19H26I3N3O9. Acceptance criteria: NMT 0.02%, based on the content of
Acceptance criteria: 95.0%–105.0% iohexol
IMPURITIES • INJECTIONS AND IMPLANTED DRUG PRODUCTS á1ñ: Meets the
• ORGANIC IMPURITIES requirements
Solution A: Acetonitrile ADDITIONAL REQUIREMENTS
O
Solution B: Water
Mobile phase: The percentage of Solution A increases from Change to read:
1% to 13% at a rate of 0.2%/min.
System suitability solution: 1.5 mg/mL, 0.0075 mg/mL, • PACKAGING AND STORAGE: Preserve Injection intended for
and 0.0069 mg/mL each of USP Iohexol RS, USP Iohexol intravascular or intrathecal use in single-dose or
Related Compound A RS, and USP Iohexol Related multiple-dose plastic or ▲preferably▲ (RB 1-Apr-2023) Type I
Compound C RS in water glass containers. Store at controlled room temperature,
Sample solution: 1.5 mg/mL of Iohexol protected from light. Do not freeze.
Chromatographic system • LABELING: Label containers of Injection to direct the user to
(See Chromatography á621ñ, System Suitability.) discard any unused portion. The labeling states also that it
Mode: LC is not to be used if it is discolored or contains a precipitate.
Detector: UV 254 nm Label it also to state its routes of administration. When the
Column: 4.6-mm × 25-cm stainless steel column; packing specific dose strength is not intended for intrathecal use,
L1 label it to indicate “serious injury can occur if given by
Flow rate: 1.0 mL/min intrathecal route”.
Injection volume: 10 µL • USP REFERENCE STANDARDS á11ñ
System suitability USP Iohexol RS
Sample: System suitability solution USP Iohexol Related Compound A RS
[NOTE—The relative retention times for the exo-isomer 5-(Acetylamino)-N,N′-bis(2,3-dihydroxypropyl)-2,4,6-
of iohexol and the O-alkylated compounds are triiodo-1,3-benzenedicarboxamide.
1.0 and between 1.1 and 1.4, respectively.] USP Iohexol Related Compound C RS
[NOTE—The peak area of iohexol related compound C N,N′-Bis(2,3-dihydroxypropyl)-5-nitro-1,3-
is 0.5% ± 0.1% compared to the total area of all the benzenedicarboxamide.
peaks in the chromatogram.]
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